Once known as a illegal street drug, new research shows that offers quick relief severe depression and may hold the key to successful treatment for other mental disorders.

Ketamine: A Promising New Option for Depression and Other Mental illnesses

Today, millions of people worldwide live with a mental illness. Research shows that roughly one in four American adults suffer from a diagnosable mental disorder in any given year. With mental health disorders expected to become one of the leading causes of death this year, experts continue to seek new treatments, particularly for disorders that are resistant to traditional therapies. And the answer may lie in an unlikely place — ketamine.

Ketamine is an anesthetic, but it is perhaps better known for its history as an illegal street drug. However, new research shows that ketamine offers quick relief for the core symptoms of severe depression and may hold the key to successful treatment for other mental disorders.

What is Ketamine?

Ketamine is a short-acting anesthetic used by veterinarians and medical practitioners. It was first developed by scientists at Parke-Davis Laboratories in 1962 as a safer derivative of phencyclidine (PCP). It is classed as a “dissociative anesthetic”, which is characterized by a trance-like state and a feeling of detachment from reality. Initially called CI-581, it was officially approved by the U.S. Food and Drug Administration (FDA) for use on humans in 1970. Due to its broad margin for error and its minimal effect on respiratory function, ketamine is commonly used as a combat anesthetic and for sedating children.

Ketamine mainly works as an ionotropic glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist. In other words, it blocks the NMDA receptor from responding, preventing communication between the brain and the spinal column to produce ketamine’s analgesic properties. At lower doses, lower than what is used in anesthesia, ketamine produces hypnosis, pain relief, and euphoria. Higher doses can result in visual and auditory hallucinations, illusions of separation from one’s environment, and mild paralysis (often referred to as a “K-hole”).

Ketamine — Potentially a Life-Saving Treatment

Despite ketamine’s reputation as a club drug, the World Health Organization has reviewed ketamine a number of times since 2004 and has repeatedly ruled against any international regulation as the results would be devastating. Ketamine as an anesthetic doesn’t require a reliable electricity supply, oxygen, or highly trained staff to administer, which makes it critical to surgery in lower-income countries or conflict zones. Currently, ketamine can be found on the WHO’s 2019 Model List of Essential Medicine, a core list of “the most efficacious, safe, and cost-effective medicines for priority conditions”.

Now, a growing body of research suggests that ketamine can be used for more than treatment of acute and chronic physical pain, it’s also been found effective for helping relieve depression symptoms as well.

In 2000, researchers at Yale Medical School published a study that found ketamine had strong, fast-acting, and long-term effects on depression. The study was small, involving a randomized, placebo-controlled, crossover design study. Patients were given 0.5mg/kg of ketamine or saline — the results showed that antidepressant effects began within four hours, peaked at 72 hours, and lasted up to two weeks after treatment.

A second study, published in 2006 by the National Institute of Mental Health (NIMH), replicated the same results with an independent group of 18 patients suffering from major depressive disorders (MDD) and resistant to other treatments. Patients who received ketamine showed improvements in symptoms within 110 minutes, with over 30 percent maintaining a response for at least one week.

And the evidence doesn’t stop there. The potential benefits of using ketamine for treating depression has become an exciting new area of research in recent years:

  • A study from Columbia University Medical Center found that patients suffering from suicidal thoughts experienced a major reduction within 24 hours of receiving a low dose of ketamine and exhibited lasting effects for an extended duration of time.
  • According to researchers at Weill Cornell Medicine, ketamine has been found to induce changes in the brain circuit function of stressed mice, improving depressed behavior within a matter of hours.
  • Another study from the Karolinska Institutet found that 70 percent of participants experienced improvements in their depression after receiving twice-weekly doses of ketamine. The drug also increased the number of serotonin 1B receptors in the brain, which are key to mood regulation.

Ketamine’s reputation is slowly moving away from that of a party drug and into a new and exciting form of treatment that could be used for severe depression and other treatment-resistant disorders. In fact, the FDA showed just how much perception has changed with its approval of a nasal spray form of ketamine called Spravato by Janssen Pharmaceuticals in March 2019.

Why is Ketamine an Effective Treatment for Depression?

One of the biggest issues with most forms of antidepressants today is their increasing ineffectiveness to offer relief for a growing number of individuals. Of the estimated 17 million American adults who live with depression, as much as one quarter of them gain little or no benefit from commonly prescribed or recommended treatments. Treatment-resistant depression is a condition when patients have failed to respond to at least two different forms of antidepressant treatments.

So, what’s different about ketamine?

Here’s why researchers believe ketamine is more effective at fighting depression than other antidepressants:

Ketamine Rewires How the Brain Functions.

The majority of antidepressants typically work by increasing chemicals in the brain, such as serotonin, norepinephrine, and dopamine. In contrast, ketamine blocks NMDA, a glutamate receptor. Glutamate is an excitatory neurotransmitter, which is responsible for making neurons more active, communicative, and flexible. And while scientists are not exactly sure of the exact mechanism yet, recent studies suggest that ketamine appears to provoke a burst of neural activity that results in stronger synaptic connections, prompting the brain to create new pathways. This makes the brain more adaptable, providing the opportunity for patients to create new behaviors and positive feelings.

Ketamine Balances Glutamate and GABA Levels.

Glutamate and Gamma Aminobutyric Acid (GABA) neurotransmitters are believed to play a major role in regulating brain activity, including mood. GABA is a calming neurotransmitter in the central nervous system. Increased levels of glutamate in the brain and a deficit in GABA receptors have been linked to a range of mental health issues, including depression and anxiety. Ketamine helps to normalize glutamate receptor levels and synapse function, which helps restore a healthy balance between glutamate and GABA levels.

Ketamine Decreases Abnormal Activity in the Lateral Habenula.

The lateral habenula is referred to as the “anti-reward center” and is an area of the brain responsible for emotional processing, specifically for difficult feelings or memories. Increasing evidence indicates that overactivity in this area of the brain is strongly linked to depression and negative emotions. Ketamine is known to reduce neural activity in the lateral habenula as it is dependent on NMDA receptors, and this may serve as the mechanism for the drug’s rapid antidepressant effects.

Ketamine Offers Rapid Relief for Anxiety, PTSD, and Addiction

In addition to depression, ketamine has also been shown to play an important role in helping to relieve anxiety disorders, post-traumatic stress disorder (PTSD), and even addiction.

Anxiety Disorders

Several studies have been conducted using ketamine to treat both general anxiety disorder (GAD) and social anxiety disorder (SAD). For instance, a study published in 2018 evaluated the use of a single dose of ketamine at weekly intervals over three months on non-depressed patients suffering from refractory GAD and/or SAD. Participants reported reduced anxiety within 1 hour of dosing, which persisted for up to a week afterwards.

Post Traumatic Stress Disorder (PTSD)

There is increasing evidence that glutamate plays a significant role in the creation of traumatic memories and the onset of PTSD. As a result, scientists have started to investigate glutamatergic interventions, such as ketamine, as a possible treatment. A Mount Sinai study found a significant and rapid reduction of PTSD symptoms within 24 hours of administering ketamine when compared to the placebo control group.

Another study studied the effects of ketamine on the enhancement of passive learning (PA) in the brains of mice after witnessing a traumatic event. The drug was found to prevent PA, suggesting it can be useful for preventing pathophysiological consequences of psychological trauma.


Evidence shows that the dissociative aspects of ketamine can help address the underlying psychology of addiction. Ketamine blocks NMDA receptors, which are also important for memory formation, helping to instill new beliefs and associations with substance abuse.

After being treated with ketamine, 66 percent patients in a 1997 study remained sober — compared to 24 percent in patients in conventional treatments. More recent studies have seen similar results of increased abstinence, reduction in relapse, and a reduced enjoyment of drinking after receiving ketamine therapy. Researchers have also been successful with using ketamine for treatment for other types of drug abuse, including heroin and cocaine addiction.

Psychedelic therapy clinics

While ketamine as a nasal spray only hit the market last year, it is already available for medical use as an anesthetic and using it for legitimate off-label purposes is not considered illegal. As a result, there has been a sharp increase in ketamine clinics offering intravenous ketamine infusions since 2015.

The rise in ketamine clinics has given way to the creation of an entirely new type of clinical practice — psychedelic therapy. Psychedelic therapy clinics seek to provide evidence-based, legal psychedelic therapy options. For example, Field Trip Health, which recently opened clinics in Toronto and New York, aims to combine personalized psychotherapy services with psychedelic medicine, such as ketamine and psilocybin therapy.

Psychedelic therapy is still very much in its nascent stages, but the outlook is promising. Ketamine, psilocybin, and ibogaine are all currently psychedelic substances that have been granted FDA approval for clinical trials. FDA recognition not only legitimizes psychedelic research, but also signals the increasingly viable possibility of more legal psychedelic treatments in the future.

Future Promise for Ketamine and Other Mental Disorders

The scope of research into ketamine’s potential has expanded to include treatment options for those dealing with severe anxiety, OCD, chronic pain issues, PTSD, and other mental disorders, offering new hope for individuals who have failed with more traditional treatment options. Further research into why ketamine acts so quickly will provide deeper insight into the mechanisms of depression, making it easier to continue developing newer treatment options that do not produce undesirable side effects.

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